It is known that desloratadine as actually used for pharmaceutical formulation has very little or no solubility in water. Another aspect of the drug is that desloratadine is not stable and shows discoloration during stability studies. These dual characteristics of the drug require non-flexible special formulation design to prevent degradation and to retain potency. It has been found (see U.S. Pat. No. 6,100,274) that in solid dosage form desloratadine, containing acidic excipients along with lactose monohydrate resulted in a large amount (14%) of decomposition after one week at 40° C. and 75% relative humidity.
The present invention provides a stable novel desloratadine hemifumarate salt with high water solubility and compatibility with a wide range of excipients for pharmaceutical formulation. The process of preparation of polymorphic form of desloratadine hemifumarate salt produces consistently high quality of the active pharmaceutical ingredient. Stochiometrically one molecule fumaric acid is combined with two molecules of desloratadine.
The invention provides pharmaceutically elegant and desirable properties needed for a drug to be administered to allergic patients, that has excellent color and thermal stability for solid dosage form and is free of undesired solvating agents such as water and organic solvents.
Related patents include:                U.S. Pat. No. 4,659,716 which discloses descarbonylethoxyloratadine possessing antihistaminic properties with substantially no sedative properties. This U.S. patent also discloses methods of making descarbonylethoxyloratadine, pharmaceutical compositions it and methods of using the compositions to treat allergic reactions in mammals. The compound is taught to form salts with fumaric acid among other pharmaceutically acceptable acids.        U.S. Pat. No. 5,595,997 discloses pharmaceutical compositions and methods for treating allergic rhinitis using descarbonylethoxyloratadine.        U.S. Pat. No. 6,100,274 pharmaceutical compositions containing descarbonylethoxyloratadihe.        PCT WO 99/01450 discloses polymorphs of descarbonylethoxyloratadine and pharmaceutical compositions containing them. The polymorph forms are different from those of this invention. Polymorphs of loratadine are disdosed in U.S. Pat. No. 6,335,347.        